Loss of 5-HT (5-hydroxytryptamine, serotonin) neurons in Parkinson's disease has been established with both direct and indirect measurements. Direct measurements are performed on postmortem material and include techniques of immunochemistry and autoradiography, measurements which can not be applied in living patients. Indirect evidence is provided by reduced concentrations of 5-HT and its metabolites in the cerebrospinal fluid. These measurements are performed in living patients, but they do not provide a direct, quantitative estimate of 5-HT neurons and axon terminals in different regions of the brain. Preliminary data indicate that it is feasible to image the 5-HT transporter in the human brain with PET and carbon-11 McN5652 and that 5-HT transporter loss can be detected in patients with Parkinson's disease using this method. The purpose of this project is to quantitatively measure 5-HT transporter loss and gain and understanding of its clinical significance in Parkinson's disease. The following specific hypotheses will be addressed: 1) Radioligand binding to the 5-HT transporter is significantly reduced in Parkinson's disease: 2) Severity of clinical manifestations of Parkinson's disease correlates with the quantitative data derived from PET measurements. The long term goal of this project is to further elucidate the role of 5-HT neuronal loss in Parkinson's disease. This should lead to a better understanding of the role of serotonin enhancing drugs in treating patients with PD.